Metabolism of tocainide in the rat.
The metabolism of tocainide, an oral antiarrhythmic agent, was studied in male Wistar rats following oral administration of 15 mg/kg of tocainide hydrochloride. Qualitative and quantitative identification of the metabolites in urine was carried out by GC-mass spectrometry and electron capture detector gas chromatography. About 15-20% of the dose administered was excreted as intact drug in the urine. An additional 20% of the dose was present as acid hydrolysable conjugates. Enzymatic hydrolysis (beta-glucuronidase) revealed half of the acid hydrolysable conjugates to be a glucuronide. The enzyme mediated hydrolysis was blocked by its specific inhibitor saccharo-1,4-lactone. N-acetyl tocainide, an oxidatively deaminated tocainide, an aldehyde adduct of tocainide, and a cyclic hydantoin derivative of tocainide were also identified as metabolites in the urine samples.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism*; D001711:Biotransformation; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008745:Methylation; D051381:Rats; D011919:Rats, Inbred Strains; D016677:Tocainide
D000889:Anti-Arrhythmia Agents; D016677:Tocainide; D008012:Lidocaine